The purpose of this grant application is to enable me to become an independent clinical researcher, with expertise in applying the techniques of functional magnetic resonance imaging (fMRI) and neuroeconomics to patients with mood and anxiety disorders. This three year grant request builds on a 2-year (K12/KL2) internal award I received from Emory in mid-2007. Active mentoring, didactic coursework, and the completion of the proposed project constitute the training components. The goal of the proposed study is to identify the neurological correlates of sensitivity to loss in major depressive disorder (MDD). This goal will be achieved by applying a neuroeconomics framework to the study of MDD. In particular, the neuroeconomics concept of "loss aversion" will be compared between depressed and control subjects. The study has two specific aims: (1) to measure and compare loss aversion among depressed patients and healthy controls;(2) to explore the association between loss aversion and patterns of neural activity within the structures of the reward system of the brain. This cross-sectional study will employ a gambling task demonstrated to differentially activate brain regions in healthy controls as they make decisions about potential gains or losses. Thirty matched pairs of moderate to severely depressed patients and healthy control subjects will be enrolled, matched on age, gender and annual income. Using money they have earned through completing testing procedures, participants will choose whether or not to accept a series of gambles that offer a potential gain or loss. These decisions will be made within an event-related trial design administered in a 3 Tesla fMRI scanner. Hypotheses for the study are that, compared with controls, depressed patients will demonstrate lower sensitivity to losses, i.e. reduced levels of loss aversion, and that these choices will correlate with smaller changes from resting state in neural activity within reward system circuitry, such as the ventral striatum and orbital frontal cortex. If proven, these hypotheses may inform our understanding of how depressed patients make choices against their best interests, and put themeselves at risk for further financial or interpersonal losses, and possibly self-directed harm. PUBLIC HEALTH RELEVANCE: People suffering from major depression often make choices about their lives that are detrimental to themselves. Understanding the biological basis of how depressed people make such choices may help clinicians prevent the harm that can arise from such detrimental decisions, such as loss of jobs, relationships, or even loss of concern for one's own life.